Abstract: Rock burst mostly occurs in the geological structure area, with variable regions of coal thickness being one of the typical geological structures. Large-diameter drilling method have become a widely adopted technique for efficient pressure relief. However, their performance within variable regions of coal thickness requires further investigation. A mechanical model for pressure relief using large-diameter drilling method was established based on the equivalent elastic modulus principle. This study analyzes the stress distribution and energy transfer patterns around large-diameter drilling holes in variable regions of coal thickness, and thereby revealing the mechanical mechanism of pressure relief and energy release in such zones. The results show that the variable rates of coal thickness significantly influence both the stress distribution around the large-diameter drilling hole and the energy release efficiency. As the variable rate of coal thickness increases from 20% to 80%, the peak tangential stress around the large-diameter drilling hole increases from 10.19 MPa to 13.09 MPa, and notably, the energy release rate improves from 22.6% to 34.0%. The high stress gradient present in variable regions of coal thickness means that the dissipation of elastic energy in the coal body is governed both by the energy released through large-diameter drilling hole and by the energy supplied from the surrounding rock layers. Importantly, higher variable rates of coal thickness lead to more effective pressure relief and energy release via large-diameter drilling hole. During the mining of the 2-2 coal seam in the 1219 working face of a coal mine, which passed through a coal seam bifurcation zone, field measurements showed that the average drilling cuttings volume was 3.96 kg/m in areas with low variable rates of coal thickness, compared to 3.34 kg/m in areas with high variation rates. This evidence further supports the conclusion that variable rates of coal thickness result in differing stress gradient distributions, which in turn affect the efficacy of pressure relief and energy release using large-diameter drilling holes in such variable regions.